Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRR474Z)

• DOT Name: Endoplasmic reticulum membrane adapter protein XK
• Synonyms: Kell complex 37 kDa component; Kx antigen; Membrane transport protein XK; XK-related protein 1
• Gene Name: XK
• Related Disease: McLeod neuroacanthocytosis syndrome
• UniProt ID: XK_HUMAN
• Pfam ID: PF09815
• Sequence:
  MKFPASVLASVFLFVAETTAALSLSSTYRSGGDRMWQALTLLFSLLPCALVQLTLLFVHR
  DLSRDRPLVLLLHLLQLGPLFRCFEVFCIYFQSGNNEEPYVSITKKRQMPKNGLSEEIEK
  EVGQAEGKLITHRSAFSRASVIQAFLGSAPQLTLQLYISVMQQDVTVGRSLLMTISLLSI
  VYGALRCNILAIKIKYDEYEVKVKPLAYVCIFLWRSFEIATRVVVLVLFTSVLKTWVVVI
  ILINFFSFFLYPWILFWCSGSPFPENIEKALSRVGTTIVLCFLTLLYTGINMFCWSAVQL
  KIDSPDLISKSHNWYQLLVYYMIRFIENAILLLLWYLFKTDIYMYVCAPLLVLQLLIGYC
  TAILFMLVFYQFFHPCKKLFSSSVSEGFQRWLRCFCWACRQQKPCEPIGKEDLQSSRDRD
  ETPSSSKTSPEPGQFLNAEDLCSA
• Function: Recruits the lipid transfer protein VPS13A from lipid droplets to the endoplasmic reticulum (ER) membrane.
• Tissue Specificity: High levels in skeletal muscle, heart, brain, and pancreas; low levels in placenta, lung, liver, and kidney.
• Reactome Pathway: Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
McLeod neuroacanthocytosis syndrome	DISA8FUX	Strong	X-linked	[1]

10 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Endoplasmic reticulum membrane adapter protein XK.	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Endoplasmic reticulum membrane adapter protein XK.	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Endoplasmic reticulum membrane adapter protein XK.	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Endoplasmic reticulum membrane adapter protein XK.	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Endoplasmic reticulum membrane adapter protein XK.	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Endoplasmic reticulum membrane adapter protein XK.	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Endoplasmic reticulum membrane adapter protein XK.	[8]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Endoplasmic reticulum membrane adapter protein XK.	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Endoplasmic reticulum membrane adapter protein XK.	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Endoplasmic reticulum membrane adapter protein XK.	[2]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Endoplasmic reticulum membrane adapter protein XK.	[10]

References

• [1] McLeod neuroacanthocytosis: genotype and phenotype. Ann Neurol. 2001 Dec;50(6):755-64. doi: 10.1002/ana.10035.
• [2] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [10] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.